This invention involves a process and compositions of the drug, bio-affecting, and body treating type. More specifically, this invention deals with a process for treatment of ocular hypertension by ocular instillation of 4-[2-(isopropylamino)ethyl]pyrocatechol.
Ocular hypertension is associated with glaucoma, a disease of the eye characterized by a progressive increase in intraocular pressure which occurs over a prolonged period of time which if untreated continues until the optic nerve is damaged and blindness results. The goal in the treatment of glaucoma is to reduce the intraocular pressure sufficiently to prevent damage to the optic nerve. The adrenergic amine epinephrine applied topically to the eye is a widely used treatment. Miotics which include certain parasympathomimetics such as pilocarpine and cholinesterase inhibitors such as physostigmine are also widely used topically. Improved drugs for topical application to the eye to reduce intraocular pressure are needed, however, due to side effects caused by existing drugs. Common undesired effects induced by the miotics include twitching of the eye lids, browache, headache, ocular pain, conjunctival congestion, etc. Localized allergy occasionally develops. Absorption of the topically applied drug occasionally causes systemic effects. This is particularly true with the cholinesterase inhibitors which may cause salivation, sweating, nausea, vomiting, bradycardia, hypotension, etc., and with adrenergic (sympathomimetic) agents which may cause tachycardia, hypertension, headaches, sweating, tremors, etc. The alpha-adrenergic stimulating action of epinephrine, for instance, frequently causes mydriasis and sometimes retinal maculopathy on prolonged usage.
Isoproterenol, an adrenergic agent whose action differs from epinephrine in that it is considered almost exclusively a beta-adrenergic stimulator, has been evaluated by Ross and Drance, Arch. Ophthal., 83, 39-43 (1970), in patients with ocular hypertension. Satisfactory reduction in intraocular pressure as a result of ocular instillation of a 5% isoproterenol hydrochloride solution was obtained but, concomitant side effects of a serious nature were also seen which prohibited the practical use of isoproterenol for glaucoma treatment. Among side effects associated with the administration of isoproterenol for reduction of intraocular pressure were marked and dangerous tachycardia of up to 100 to 150 beats per minute as well as palpitations, a nervous feeling, and weakness.
F. E. Leaders, et al., Arch. Int. Pharmacodyn., 183, 93-106 (1970), in reporting a study of the mydriatic and ocular hypotensive effects of selected phenethylamine derivatives, indicated that dopamine hydrochloride reduces intraocular pressure in the rabbit eye induced by topical application of 2.5% formalin according to the test method of B. Fortenberry, et al., Proc. Soc. Exp. Biol., New York, 131, 637 (1969).